L Bresciani1, L Calani1, L Bocchi2, F Delucchi2, M Savi2, S Ray3, F Brighenti4, D Stilli5, D Del Rio6. 1. The φ(2) Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, 43125 Parma, Italy; LS9 Bioactives and Health, Interlab Group, Department of Food Science, University of Parma, Parma, Italy. 2. Department of Life Sciences, University of Parma, 43124 Parma, Italy. 3. Cambridge University Hospitals and School of Clinical Medicine, Cambridge, UK. 4. The φ(2) Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, 43125 Parma, Italy. 5. Department of Life Sciences, University of Parma, 43124 Parma, Italy. Electronic address: donatella.stilli@unipr.it. 6. The φ(2) Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, 43125 Parma, Italy; LS9 Bioactives and Health, Interlab Group, Department of Food Science, University of Parma, Parma, Italy. Electronic address: daniele.delrio@unipr.it.
Abstract
BACKGROUND AND AIMS: Trans-resveratrol (RSV) is a natural compound occurring in different foods and plants, which in vivo is rapidly conjugated with glucuronic acid and sulfate. Despite its demonstrated cardioprotective activity, the bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown. METHODS AND RESULTS: Diabetic rats were randomized to 1, 3 or 6 weeks of RSV treatment at two different doses (1 or 5 mg/kg/day). A dose and time-dependent accumulation was observed, with no detectable levels of RSV metabolites found in heart tissues after 1 week and significant concentrations of RSV-3-sulfate and RSV-3-glucuronide after 6 weeks of treatment (0.05 nmol/g of tissue and 0.01 nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was accompanied by an improvement of cardiac function in long-term diabetes, when myocardial morpho-functional damage is more evident, with an almost complete recovery of all hemodynamic parameters, at the highest RSV dose. CONCLUSION: Even if a higher concentration of RSV in tissues cannot be ruled out after constant oral administration, an accumulation coherent with what is usually evaluated in cell based mechanistic studies is largely unattainable and the RSV unconjugated form would not be present in this paradigm. The current investigation provides data on myocardial tissue concentrations of RSV metabolites, after short/medium term RSV treatment. This knowledge constitutes a basic requirement for future studies aimed at reliably defining the molecular pathways underlying RSV-mediated cardioprotective effects and opens up new perspectives for research focused on testing phenolic compounds as adjuvants in degenerative heart diseases.
BACKGROUND AND AIMS: Trans-resveratrol (RSV) is a natural compound occurring in different foods and plants, which in vivo is rapidly conjugated with glucuronic acid and sulfate. Despite its demonstrated cardioprotective activity, the bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown. METHODS AND RESULTS:Diabeticrats were randomized to 1, 3 or 6 weeks of RSV treatment at two different doses (1 or 5 mg/kg/day). A dose and time-dependent accumulation was observed, with no detectable levels of RSV metabolites found in heart tissues after 1 week and significant concentrations of RSV-3-sulfate and RSV-3-glucuronide after 6 weeks of treatment (0.05 nmol/g of tissue and 0.01 nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was accompanied by an improvement of cardiac function in long-term diabetes, when myocardial morpho-functional damage is more evident, with an almost complete recovery of all hemodynamic parameters, at the highest RSV dose. CONCLUSION: Even if a higher concentration of RSV in tissues cannot be ruled out after constant oral administration, an accumulation coherent with what is usually evaluated in cell based mechanistic studies is largely unattainable and the RSV unconjugated form would not be present in this paradigm. The current investigation provides data on myocardial tissue concentrations of RSV metabolites, after short/medium term RSV treatment. This knowledge constitutes a basic requirement for future studies aimed at reliably defining the molecular pathways underlying RSV-mediated cardioprotective effects and opens up new perspectives for research focused on testing phenolic compounds as adjuvants in degenerative heart diseases.